To investigate the effect of exercise on the function of bone marrow endothelial cells in type 2 diabetic mice based on intestinal flora

Abstract:

Objective To investigate whether aerobic exercise combined with resistance exercise can improve the diversity，abundance and structure of intestinal beneficial flora and its effect on the function of bone marrow endothelial progenitor cells（EPCs） in type 2 diabetic mice.Methods Forty 8-week-old male db/db mice were randomly divided into control group（DZ group）. Diabetic model + aerobic and resistance exercise group（combined exercise）（L group），diabetic model + fecal transplantation group（SY group），and diabetic model group（TJ group），with 10 rats in each group. Group L carried out aerobic exercise combined with resistance exercise for 8 weeks，aerobic exercise on Monday，Wednesday and Friday，and resistance exercise on Tuesday，Thursday and Saturday，6 days/W. In SY and TJ groups，the feces of mice in group L and DZ after 8 weeks of exercise were made into suspension，respectively，and then enema was given twice a day for 14 days. After the end of enema，the proliferation，migration，adhesion and angiogenesis ability of bone marrow EPCs in each group were detected. The EPCs phenotypes CD34 and CD31 were identified by flow cytometry，and the abundance and diversity of intestinal flora in feces were detected by 16SrRNA. ELISA was used to detect serum glucagon-like peptide1（GLP-1） in each group.Results At the class level，the abundance of Clostridia（54.60% vs. 32.21%） and Bacteroidia（47.63% vs. 36.39%） in the SY group was higher than that in the TJ group. The abundance of Gammaproteobacteria（0.30% vs. 12.57%） was significantly decreased（P=0.019，P=0.028，P=0.002）. Compared with DZ group，the abundance of Bacteroidia in SY group increased（47.63% vs. 38.5%），and the abundance of Bacilli decreased（2.56% vs. 12.36%），and the difference was statistically significant（P=0.021，P=0.039）. At the family level，the abundance of Lachnospiraceae（43.86% vs. 26.44%） and Oscillospiraceae（7.8% vs. 2.15%） in the SY group was significantly higher than that in DZ group（P=0.004，P=0.001）. Compared with the TJ group，The abundance of Lachnospiraceae（43.86% vs. 32.89%），Lactobacillaceae（9.89% vs. 3.8%） and Oscillospiraceae（7.8% vs. 2.21%） in the intestinal tract of SY group was significantly increased（P=0.045，P=0.006，P=0.001）. The proliferation，migration，adhesion and angiogenesis of EPCs in SY group were significantly higher than those in DZ group and TJ group（P=0.002，P=0.000，P=0.000，P=0.000，P=0.016，P=0.049，P=0.019，P=0.026）. The content of serum glucagon peptide-1（GLP-1）（pmmol/L） in DZ group SY and TJ group（1.90±0.22，2.82±0.40 and 2.24±0.49） was significantly different（F=31.082，P=0.000）. Compared with DZ group，the serum GLP-1 level in SY group was significantly increased（P=0.000）. Compared with TJ group，the serum GLP-1 level in SY group was significantly increased（P=0.000）. The correlation analysis between the number of intestinal flora and the function of endothelial cells showed that：Clostridia（r=0.696，P=0.041），Oscillospiraceae（r=0.697，P=0.037） Muribaculaceae was positively correlated with cell migration（r=0.753，P=0.019） and angiogenesis（r=0.810，P=0.008） in the endothelial group.Conclusion Aerobic exercise combined with resistance exercise may improve the function of EPCs in bone marrow of type 2 diabetic mice by increasing the abundance，diversity and structure of beneficial intestinal bacteria and increasing the expression of GLP-1.